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Purity: =98.69%
AZD7545 is a novel, potent, selective small-molecule inhibitor of PDHK (pyruvate dehydrogenase kinase 2) with IC50 of 36.8 nM and 6.4 nM for PDHK1 and PDHK2, respectively. Additionally, using recombinant human PDHK2, AZD7545 boosts PDH activity with an EC50 value of 5.2nM. The administration of AZD7545 significantly increases PDH activity in the liver and only slightly increases PDH activity in the heart and skeletal muscle, according to in vivo studies. An increase in muscle PDH from 61% to 97% active and liver PDH from 33.5% to 72.8% is seen in Zucker (fa/fa) rats when given AZD7545 at a dose of 10 mg/kg.
| Targets |
PDHK2 (IC50 = 6.4 nM); PDHK1 (IC50 = 36.8 nM);
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| ln Vitro |
AZD7545 (10 μM; 90 hours for BRAF V600E human melanoma cells and 120 hours for NRASmut human melanoma cells) specifically inhibits the growth of cells with BRAF and NRAS mutations as well as in inhibitor-resistant human melanoma[2].
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| ln Vivo |
A single dose of AZD7545 (Oral administration; 10 mg/kg once daily (08:00 h) or twice daily (08:00 and 18:00 h); for 7 days) increases the proportion of liver PDH in its active, dephosphorylated form in a dose-related manner in Wistar rats. In obese Zucker (fa/fa) rats, a single 10 mg/kg dose also significantly increases muscle PDH activity[3].
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| Animal Protocol |
Obese male (fa/fa) Zucker rats[3];
10 mg/kg; Oral administration; once a day (08:00 h) or Twice a day ( 08:00 and 18:00 h); for 7 days; |
| References |
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| Additional Infomation |
AZD7545 is a sulfone that is benzene substituted by [4-(dimethylcarbamoyl)phenyl]sulfonyl, chloro and [(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]amino groups at positions 1, 3 and 4, respectively. It is a potent and non-ATP-competitive inhibitor of pyruvate dehydrogenase kinase 2 (PDHK2) with IC50 of 6.4 nM and exhibits glucose-lowering activity. Also inhibits PDHK1 at higher levels (IC50 = 36.8 nM). It has a role as a hypoglycemic agent and an EC 2.7.11.2 - [pyruvate dehydrogenase (acetyl-transferring)] kinase inhibitor. It is a member of benzamides, a sulfone, a tertiary alcohol, a tertiary carboxamide, a secondary carboxamide, a member of monochlorobenzenes and an organofluorine compound.
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| Molecular Formula |
C19H18CLF3N2O5S
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| Molecular Weight |
478.87
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| Exact Mass |
478.057
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| Elemental Analysis |
C, 47.66; H, 3.79; Cl, 7.40; F, 11.90; N, 5.85; O, 16.71; S, 6.69
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| CAS # |
252017-04-2
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| Related CAS # |
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| PubChem CID |
16741245
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
683.1±55.0 °C at 760 mmHg
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| Flash Point |
366.9±31.5 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.573
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| LogP |
2.66
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
31
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| Complexity |
778
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| Defined Atom Stereocenter Count |
1
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| SMILES |
ClC1C([H])=C(C([H])=C([H])C=1N([H])C([C@](C([H])([H])[H])(C(F)(F)F)O[H])=O)S(C1C([H])=C([H])C(C(N(C([H])([H])[H])C([H])([H])[H])=O)=C([H])C=1[H])(=O)=O
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| InChi Key |
DTDZLJHKVNTQGZ-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C19H18ClF3N2O5S/c1-18(28,19(21,22)23)17(27)24-15-9-8-13(10-14(15)20)31(29,30)12-6-4-11(5-7-12)16(26)25(2)3/h4-10,28H,1-3H3,(H,24,27)/t18-/m1/s1
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| Chemical Name |
4-[3-chloro-4-[[(2R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanoyl]amino]phenyl]sulfonyl-N,N-dimethylbenzamide
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.22 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0882 mL | 10.4412 mL | 20.8825 mL | |
| 5 mM | 0.4176 mL | 2.0882 mL | 4.1765 mL | |
| 10 mM | 0.2088 mL | 1.0441 mL | 2.0882 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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